Sj"gren's syndrome is one of the most prevalent rheumatic autoimmune disease affecting approximately 4 million people in this country, mostly women reaching middle age. The disease is caused by chronic inflammation of the lachrymal and salivary glands, resulting in persistent dry eyes and mouth and systemic problems involving many other organs such as joints, kidney, and lung. Work carried out in my laboratory demonstrated that Id3-/- mice develop primary Sj"gren's syndrome. This mouse model provides a unique genetic tool for further understanding the cause of Sj"gren's syndrome. Our most recent studies of Id3 deficient mice indicate that 34 T cells play a role in this disease model. This novel finding is particularly interesting given that 34 T cells in Sj"gren's syndrome have been implicated in clinical case reports. We plan to use an Id3 conditional allele to investigate lineage and stage specific requirement of Id3 in disease development. Results from the proposed studies should establish a causal link between function of Id3 in specific cell lineage at specific stage of development and Sj"gren's syndrome. The involvement of 34 T cell in this disease model, if proves to be true, would be particularly novel and point to a new direction in clinical applications. RELEVANCE: This proposal is in response to the program announcement (PA-07-336) from National Center for Research Resources, which calls for Development of Animal Models and Related Biological Materials for Research. We plan to build a new animal model for studying Sj"gren's syndrome and make this model available for scientific community for relevant research. Sj"gren's syndrome is one of the most prevalent rheumatic autoimmune disease affecting approximately 4 million people in this country, mostly women reaching middle age. The disease is caused by chronic attack of the lachrymal and salivary glands by immune cells resulting in persistent dry eyes and mouth. Work carried out in my laboratory demonstrated that Id3 deficient mice develop primary Sj"gren's syndrome. However, the disease mechanism in this animal model is currently unknown. Our most recent work led to a new hypothesis that loss of Id3 in 34 T cells may be sufficient to initiate Sj"gren's syndrome. To test this hypothesis and to build a more defined animal model, we plan to create Id3 conditional knockout mouse which eliminates Id3 exclusively in 34 T cells. We will assess phenotypes relevant to Sj"gren's syndrome in this new animal model. [unreadable] [unreadable]